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Hepatitis B virus genotype B with G1896A and A1762T/G1764A mutations is associated with hepatitis B related acute-on-chronic liver failure

Authors

  • Lei Xiao,

    1. Hepatology Unit and Key Lab for Organ Failure Research, Nanfang Hospital, Southern Medical University, Guangzhou, China
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  • Bin Zhou,

    1. Hepatology Unit and Key Lab for Organ Failure Research, Nanfang Hospital, Southern Medical University, Guangzhou, China
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  • Hongbo Gao,

    1. Department of Severe Hepatopathy, The Eighth People's Hospital of Guangzhou, Guangzhou, China
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  • Shiwu Ma,

    1. Hepatology Unit and Key Lab for Organ Failure Research, Nanfang Hospital, Southern Medical University, Guangzhou, China
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  • Guifeng Yang,

    1. Hepatology Unit and Key Lab for Organ Failure Research, Nanfang Hospital, Southern Medical University, Guangzhou, China
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  • Min Xu,

    1. Department of Severe Hepatopathy, The Eighth People's Hospital of Guangzhou, Guangzhou, China
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  • William G.H. Abbott,

    1. Hepatology Unit and Key Lab for Organ Failure Research, Nanfang Hospital, Southern Medical University, Guangzhou, China
    2. The New Zealand Liver Transplant Unit, Auckland City Hospital, Private Bag, Auckland, New Zealand
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  • Jinjun Chen,

    1. Hepatology Unit and Key Lab for Organ Failure Research, Nanfang Hospital, Southern Medical University, Guangzhou, China
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  • Jian Sun,

    1. Hepatology Unit and Key Lab for Organ Failure Research, Nanfang Hospital, Southern Medical University, Guangzhou, China
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  • Zhanhui Wang PhD,

    Corresponding author
    1. Hepatology Unit and Key Lab for Organ Failure Research, Nanfang Hospital, Southern Medical University, Guangzhou, China
    • Hepatology Unit and Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China.
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  • Jinlin Hou MD

    Corresponding author
    1. Hepatology Unit and Key Lab for Organ Failure Research, Nanfang Hospital, Southern Medical University, Guangzhou, China
    • Hepatology Unit and Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China.
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Abstract

The existence of statistical associations between hepatitis B-related acute-on-chronic liver failure and both hepatitis B virus (HBV) genotype and mutations in the basal core promoter (BCP) and precore (PC) regions needs to be confirmed. A total of 322 patients with a chronic HBV infection, including 77 with hepatitis B-related acute-on-chronic liver failure, 109 with hepatocellular carcinoma (HCC) and 136 with chronic hepatitis B (CHB) were enrolled. The HBV genotype and the presence of mutations in the BCP/PC regions were determined by direct sequencing, and the frequencies were compared in the three patient groups. Overall, 198/322 (61.5%) were infected with genotype B and 124/322 (38.5%) with genotype C. Genotype B was significantly more frequent in patients with acute-on-chronic liver failure than CHB (92.2% vs. 60.3%, P < 0.001). As a contrast, genotype C was more common in patients with HCC than CHB (58.7% vs. 39.7%, P = 0.003). In genotype B patients, the A1762T/G1764A, A1846T, and G1896A mutations were significantly more prevalent in patients with acute-on-chronic liver failure than CHB (50.7% vs. 28.0%, P = 0.004; 59.2% vs. 34.1%, P = 0.002; 69.0% vs. 41.5%, P = 0.001, respectively). In multivariate analysis, the risk factors for acute-on-chronic liver failure were genotype B, A1762T/G1764A, and G1896A. In conclusion, CHB patients with genotype B, G1896A, and A1762T/G1764A had a higher tendency to develop liver failure than patients with genotype C. Therefore, HBV genotyping and detecting G1896A and A1762T/G1764A mutations might have important clinical implications as predictive risk factors for hepatitis B-related acute-on-chronic liver failure. J. Med. Virol. 83:1544–1550, 2011. © 2011 Wiley-Liss, Inc.

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